--- title: "ENG S328X (c.983_984delinsAG, rs1588581338) | Dante Labs" description: "ClinVar classifies ENG S328X as Pathogenic (criteria provided, multiple submitters, no conflicts). Where it sits in the genome, its predicted effect, and the Genome Test reports that look at it." url: "https://dantelabs.com/genes/eng/variants/s328x" --- 1. [Genes](https://dantelabs.com/genes) 2. [ENG](https://dantelabs.com/genes/eng) 3. ENG S328X Variant # ENG S328X NM_001114753.3(ENG):c.983_984delinsAG (p.Ser328Ter) Also known as - p.Ser328Ter - p.S328\* - rs1588581338 * ClinVar classification Pathogenic * Review status 2 stars out of 4 criteria provided, multiple submitters, no conflicts * Last evaluated 30 March 2023 Data current to ClinVar release 2026-10-19 · Dante Labs data release 2026.10.21-777c9289 Facts last changed 21 October 2026 ## Summary S328X is a nonsense variant in ENG: it creates an early stop signal, so the protein the gene encodes is predicted to be cut short. ClinVar classifies it as pathogenic for Hereditary Hemorrhagic Telangiectasia (criteria provided, multiple submitters, no conflicts). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------- | --------------------------------------------------------------------- | ------------- | -------------- | | [Hereditary Hemorrhagic Telangiectasia](https://dantelabs.com/conditions/hereditary-hemorrhagic-telangiectasia) [ClinVar VCV000665098 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/665098/) | Pathogenic | 2 stars out of 4 criteria provided, multiple submitters, no conflicts | 2 submissions | 30 March 2023 | Classifications as ClinVar records them in release 2026-10-19. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria S328X meets, from its predicted effect in ENG, gnomAD and ClinVar. | Criterion | Strength | Points | Rests on | | ------------------------------------------------------- | ----------- | ----------- | -------------------------------------------------------------------------- | | PVS1 Null variant where loss of function causes disease | Very strong | +8 | stop_gained on NM_001114753.3Expected to cause nonsense-mediated decay | | PM2 Absent or very rare in population databases | Supporting | +1 | Not seen in gnomAD exomes, gnomAD genomes | | PP5 A reputable source reports it as pathogenic | Supporting | Not counted | ClinVar: Pathogenic (criteria provided, multiple submitters, no conflicts) | On these criteria alone: +9 points, likely pathogenic. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## Population frequency How often S328X is seen among the people whose exomes and genomes gnomAD 4.1 brings together. | Dataset | Allele frequency | Allele count | Homozygotes | Commonest in | | -------------- | ---------------- | ------------ | ----------- | ------------ | | gnomAD exomes | Not seen | 0 of 0 | 0 | | | gnomAD genomes | Not seen | 0 of 0 | 0 | | Figures from gnomAD 4.1, as gnomAD publishes them. Groups are genetic ancestry groups as gnomAD infers them. They describe the variant in gnomAD's populations, not anyone's result. [S328X in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/9-127824807-GG-CT?dataset=gnomad_r4) ## Where it lies in ENG S328X lies in exon 7 of the 15 in ENG's MANE Select transcript, NM_001114753.3. [ENG variants in exon 7 →](https://dantelabs.com/genes/eng/variants?exon=7) [ENG's gene diagram →](https://dantelabs.com/genes/eng#gene-structure) ## Molecular details | Gene | [ENG](https://dantelabs.com/genes/eng) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_001114753.3 MANE Select | | Coding DNA change (HGVS c.) | c.983_984delinsAG | | Protein change (HGVS p.) | p.Ser328Ter p.S328\* | | Predicted consequence | Nonsense (stop gained) [stop_gained (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001587) | | Predicted impact | High | | Position (GRCh38) | chr9:127824807 GG>CT | | Position (GRCh37) | chr9:130587086 GG>CT | | dbSNP ID | [rs1588581338 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs1588581338) | | ClinVar Variation ID | [VCV000665098 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/665098/) | | ClinVar Allele ID | 637688 | | ClinGen Allele Registry ID | [CA915947173 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA915947173) | | ClinVar name | NM_001114753.3(ENG):c.983_984delinsAG (p.Ser328Ter) | ## ENG S328X in other databases - [ClinVar VCV000665098 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/665098/) - [dbSNP rs1588581338 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs1588581338) - [ClinGen Allele Registry CA915947173 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA915947173) - [gnomAD 9-127824807-GG-CT (opens in a new tab)](https://gnomad.broadinstitute.org/variant/9-127824807-GG-CT?dataset=gnomad_r4) - [Ensembl rs1588581338 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs1588581338) ## Reports that look at this variant (1) These Genome Test condition reports include S328X among the variants they look at. | Report | Conditions | Inheritance | | --------------------------------------------------------------------------------------------------------------- | ------------------------------------- | ------------------ | | [Hereditary Hemorrhagic Telangiectasia](https://dantelabs.com/conditions/hereditary-hemorrhagic-telangiectasia) | Hereditary Hemorrhagic Telangiectasia | Autosomal dominant | | | Telangiectasis | | ## Other variants in ENG - [c.2T>G Pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/c-2t-g) - [C382Y Pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/c382y) - [C549G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/c549g) - [G331S Pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/g331s) - [G603R Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/g603r) - [L221P Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/l221p) - [L506H Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/l506h) - [N423S Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/n423s) - [R529H Pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/r529h) - [V440G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/eng/variants/v440g) [All ENG variants](https://dantelabs.com/genes/eng/variants) ## Limitations This page describes publicly available information about a genetic variant. It is not a diagnosis, and it says nothing about whether you or anyone else carries this variant. Classifications come from ClinVar and change as new evidence is reviewed. A classification here may differ from the one in ClinVar today, or from the one a laboratory reports. Whole genome sequencing with short reads can miss or miscall some variants, particularly in repeated or highly similar stretches of DNA and in large insertions, deletions or rearrangements. If you have questions about a variant in your own results or in your family, talk to a genetic counsellor or your doctor. ## Sources & credits - Classifications from ClinVar (release 2026-10-19), National Center for Biotechnology Information. - Condition terms from the Mondo Disease Ontology (release 2026-10-06), used under CC BY 4.0. - Gene symbols and names from the HUGO Gene Nomenclature Committee (release 2026-10-16). - Allele identifiers from the ClinGen Allele Registry (release 2026-10-21-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-21). - Difficult regions from the Genome in a Bottle Consortium (release v3.6). - Transcripts from MANE (release v1.5), NCBI and EMBL-EBI. - Predicted consequences from mehari (release 0.11.0), with transcript models from cdot. - Built from Dante Labs data release 2026.10.21-777c9289 of 21 October 2026. ## Cite this page APA > Dante Labs. (21 October 2026). ENG S328X (c.983_984delinsAG, rs1588581338) (Version 2026.10.21-777c9289). Retrieved 21 October 2026, from https\://dantelabs.com/genes/eng/variants/s328x Vancouver > Dante Labs. ENG S328X (c.983_984delinsAG, rs1588581338) \[Internet]. Version 2026.10.21-777c9289. 21 October 2026 \[cited 21 October 2026]. Available from: https\://dantelabs.com/genes/eng/variants/s328x Download citation [RIS](https://dantelabs.com/genes/eng/variants/s328x/cite.ris) [BibTeX](https://dantelabs.com/genes/eng/variants/s328x/cite.bib) [CSL-JSON](https://dantelabs.com/genes/eng/variants/s328x/cite.json) ## Read your whole genome From $449 Free shipping · Results in 6–8 weeks [Explore the Genome Test](https://dantelabs.com/whole-genome-sequencing)